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21 Cards in this Set
- Front
- Back
What happens in PHase II metabolism reactions?
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Conjugation of an endogenous chemical group to a drug or drug metabolite
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What are 4 major types of conjugation reactions in Phase II metabolism?
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-Glucuronidation
-Acetylation -Sulfation -Glutathione conjugation |
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In what order do the metabolism reactions occur?
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Any order - depends on the drug and its functional groups and available enzymes
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What is required of the endogenous chemical group in order for conjugation to occur?
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It must be a High Energy intermediate
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What is the high E intermediate for:
-Glucuronidation -Acetylation -Sulfation -GSH conjugation |
Glucur - UDP-glucuronic acid
Acetyln - Acetyl-CoA Sulfation - PAPS -GSH conj - The drug itself |
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What enzyme catalyzes Glucuronidation? Where is it located?
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UDP-glucuronosyl transferases UGT - in ER lumen
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What enzyme catalyzes Acetylation? Where is it located?
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N-acetyltransferase - in the cytosol
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What enzyme catalyzes Sulfation? Where is it located?
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Sulfotransferase (SULT) - in the cytosol
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What enzyme catalyzes Glutathione conjugation? Where is it located?
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Glutathione S-transferase (GST)
-In the cytosol and some ER |
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What is the nature of metabolies generated by Phase II reactions?
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-More polar
-Inactive or less toxic |
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What are the 2 exceptions to drug metabolites of Phase II reactions being more polar?
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-Acetyltransferases
-Methyltransferases These metabolites can be LESS polar! |
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What is the substrate specificity of Phase II enzymes like?
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Broad - enzymes look for functional groups
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What are some phase II enzymes?
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Inducible
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What are the kinetics of phase II enzymes?
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Conventional michaelis menton
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What is the Vmax of phase II enzymes limited by?
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-Supply of conjugation materials
-Conventional enzyme kinetics |
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What induces an inducible enzyme?
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Increasing drug concentration (substrate)
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What type are most conjugation reactions catalyzed by?
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UDP-glucuronosyltransferase (UGT)
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Do phase II enzymes only act on drugs?
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No they can also act on endogenous compounds
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For which type of conjugation reaction is there
-High capacity -High raw material supply |
Glucuronidation (UGT)
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For which type of conjugation reaction is there
-Variable capacity -Variable raw material supply |
Acetylation
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For which types of conjugation reactions is there
-Low capacity -Low raw material supply |
-Sulfation
-Glutathione conjugation |